Lafora disease

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Portrait of Gonzalo Rodríguez Lafora .

The Lafora disease , also Lafora inclusion body disease , is a genetic disease , to the group of progressive myoclonus epilepsies and Polyglukosankrankheiten belongs. It is characterized by the occurrence of myoclonus epilepsy , hallucinations and dementia . Lafora disease manifests itself in late childhood or adolescence. The disease was first described in 1911 by Gonzalo Rodríguez Lafora (1886–1971) and Bernard Glueck . This disease can also occur in dogs such as the beagle .

Pathogenesis

The cause of the development of Lafora disease are mutations in the genes EPM2A and NHLRC1 (synonym: EPM2B ) in 80 percent of cases . The EPM2A gene codes for laforin , an enzyme from the group of phosphatases . The NHLCR1 gene codes for the E3 ubiquitin protein ligase NHLRC1 , also known as malin. In 20 percent of cases, the causative gene or mutation is not yet known.

Symptoms

Clinically, two sub-forms can be distinguished. In classic Lafora disease, the clinical symptoms begin in children and adolescents aged 6 to 19 years (peak around the age of 15) with stimulus-dependent generalized tonic-clonic seizures, absenteeism , myoclonic seizures or partial seizures with visual hallucinations and status epileptici , followed by dementia degradation and neurological deterioration, including resting and action myoclonus. In atypical Lafora disease, dyslexia and learning disabilities occur in childhood , followed by epilepsy and neurological deterioration.

diagnosis

If Lafora disease is suspected, a sample is taken from the skin ( skin biopsy ). In the microscopic examination of the biopsy, so-called Lafora bodies or inclusion bodies can be detected. In addition to being found in the skin, they are also present in muscle, brain, liver and sweat gland cells. The next step is a molecular genetic analysis of the genes mentioned above.

therapy

The disease has not yet been cured. Anti-epileptic drugs such as valproic acid and muscle relaxants such as clonazepam are prescribed to relieve symptoms . Piracetam and related substances can also be used in progressive myoclonic epilepsy. A small series with perampanel showed a good effect of this anticonvulsant. In advanced cases, one can stomach tube of aspiration pneumonia prevention (pneumonia if swallowed).

Individual evidence

  1. ^ A b W. Paulus, JM Schröder: Neuropathology. 3. Edition. Springer Verlag, 2011, ISBN 978-3-642-02323-1 , p. 169.
  2. ^ Gonzalo R. Lafora, Bernard Glueck: Contribution to the histopathology of myoclonic epilepsy. In: Journal for the whole of neurology and psychiatry. 6, 1911, pp. 1-14, doi: 10.1007 / BF02863929 .
  3. ^ A b W. Paulus, JM Schröder: Neuropathology. 3. Edition. Springer Verlag, 2011, ISBN 978-3-642-02323-1 , p. 170.
  4. ↑ Entry on E3 ubiquitin-protein ligase NHLRC1 in the UniProt Q6VVB1 database
  5. ^ A b Günter Krämer: Small Lexicon of Epileptology . Georg Thieme, Stuttgart 2005, ISBN 3-13-133831-8 .
  6. ↑ AC Jansen, E. Andermann: Progressive Myoclonus Epilepsy, Lafora Type. In: GeneReviews. December 28, 2007, update January 22, 2015 (accessed September 22, 2016)
  7. ^ D. Goldsmith, BA Minassian: Efficacy and tolerability of perampanel in 10 patients with Lafora disease. In: Epilepsy and Bahavior. 62, Sep 2016, pp. 132-135. PMID 27459034 . doi: 10.1016 / j.yebeh.2016.06.041

further reading

  • AC Jansen, E. Andermann: Progressive Myoclonus Epilepsy, Lafora Type. In: GeneReviews. University of Washington, Seattle, Seattle (WA) 1993-2007, updated November 3, 2011. PMID 20301563
  • S. Singh, S. Ganesh: Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes. In: Human mutation. Volume 30, Number 5, May 2009, pp. 715-723. ISSN  1098-1004 . doi: 10.1002 / humu.20954 . PMID 19267391 .
  • S. Ganesh, R. Puri et al .: Recent advances in the molecular basis of Lafora's progressive myoclonus epilepsy. In: Journal of human genetics. Volume 51, Number 1, 2006, pp. 1-8. ISSN  1434-5161 . doi: 10.1007 / s10038-005-0321-1 . PMID 16311711 .

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